Chronic obstructive pulmonary disease afflicts 12-14 million people in the US and in an advanced form, emphysema, disables 2 million and ultimately leads to death. No approved, existing treatment can arrest emphysema's progressive destruction of the lung. Exhale Therapeutics, Inc intends to develop and commercialize aerosolized hyaluronic acid (HA) into the first effective therapeutic product that can preserve lung function. The long-term objectives of the proposed project (Phases I) are: (1) to show that aerosolized low-molecular weight HA inhaled daily protects against lung elastic fiber injury and subsequent destruction of alveoli; and (2) to elucidate the protective mechanism. The specific aim of Phase I is to demonstrate that in mice exposed regularly to tobacco smoke in a chamber that simulates cigarette smoking, daily treatment with HA administered as an aerosol significantly reduces the severity of emphysematous damage to their lungs. Two groups of mice will smoke, the first will receive daily treatment with HA dissolved in distilled water, and the second will receive nebulized water only. A comparison of the mean linear intercept of lung sections of the two groups will provide a direct quantitative measure of the protective effect of HA. Other semi-quantitative measures will provide supporting evidence. PROPOSED COMMERCIAL APPLICATION: Hyaluronic acid (HA) has the potential to become an effective therapeutic agent that can protect lung function against the chronic destruction of alveoli in emphysema. Since no treatment for pulmonary emphysema currently exists, proof of safety and efficacy in humans will permit rapid commercialization. The proposed research in an animal model will accelerate the formulation of a therapeutic product for study and use in humans.